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Biomedical subjects

T T Nguyen

Publications and source records attributed to T T Nguyen.

At least 217 records · Page 12Linked to original sources
PubMed1991

Ventilatory response to sustained hypoxia during exercise.

The ventilatory stimulating effects of hypoxia occurring at carotid bodies are potentiated by exercise. However, hypoxia also has central ventilatory depressive effects; the potential interactions between this hypoxic depression and exercise have not been studied. We examined the ventilatory response to a 20 min period of isocapnic hypoxia (end-tidal O2, PETO2, of 50 mm Hg), preceded and followed by a 5 min period of isocapnic hyperoxia in seven normal adult males at rest and during moderate exercise (45-75 W). When hypoxia was introduced at rest (PETO2 = 42 mmHg), ventilation initially increased from 13.73 +/- 3.04 (mean +/- SD) to 23.69 +/- 5.48 1.min-1 and then slowly declined to 19.01 +/- 4.68 1 min-1. The increase was caused by increases in tidal volume and respiratory frequency, but the decline was solely in tidal volume. During a background of moderate exercise (PETCO2 = 46 mmHg), introduction of hypoxia caused ventilation to increase from 30.84 +/- 6.31 to 56.44 +/- 10.58 1.min-1. Ventilation subsequently did not decline; at the end of the hypoxic period, ventilation was 57.06 +/- 12.59 1.min-1. The increase was also associated with an increase in tidal volume and respiratory frequency, as seen as rest, but with much larger magnitudes. Despite the absence of ventilatory decline, there was still a decline in tidal volume, but it was compensated by an increase in respiratory frequency. We conclude that exercise potentiated the acute ventilatory response to hypoxia by modifying both tidal volume and respiratory frequency but that exercise abolished or greatly reduced hypoxic decline by increasing respiratory rate.

Adult↗
PubMed1990

Molecular dosimetry of polycyclic aromatic hydrocarbon epoxides and diol epoxides via hemoglobin adducts.

Ten reactive metabolites of five polycyclic aromatic hydrocarbons and styrene were investigated to determine the generality of ester adduct formation with human hemoglobin in the form of RBC and hydrolysis to the corresponding tetrahydrotetrols or dihydrodiols. No exceptions were noted among the compounds tested, which included the anti-diol epoxides of benzo[a]pyrene (BaP), chrysene, and benz[a]anthracene; the syn-diol epoxide of BaP; a mixture of syn- and anti-diol epoxides of benzo[e]pyrene; and epoxides of styrene, benzo[e]pyrene, BaP, and cyclopenta[c,d]pyrene. A test of the propensity of the simplest benzylic epoxide, styrene oxide, to form esters that hydrolyze via a BAL1 mechanism was performed. Hydrolysis of styrene oxide-adducted hemoglobin in H2(18)O at neutral pH yielded 18O incorporation results that suggest this mechanism of hydrolysis is operant to a minor degree in styrene oxide-hemoglobin ester adducts. A method was developed for the isolation and quantification of the polycyclic aromatic alcohols, which consists of enzymatic proteolysis, immunoaffinity chromatography, and gas chromatography-mass spectrometry or fluorimetry. The method allows for routine analysis of hemoglobin from individual samples as small as 1 ml of whole blood. Analysis of blood from different human populations revealed that hemoglobin adducts of the anti-diol epoxide of BaP dominated the spectrum of adducts formed by the selected metabolites.

Chromatography, Affinity↗
PubMed1989

Bidimensional reversed-phase high-pressure liquid chromatography analysis of cultured cell neuropeptides: application to atrial natriuretic factor.

We report here a one-step procedure for extraction and analysis of neuropeptides in chromaffin cell culture media and acid extracts using reversed-phase HPLC. The bidimensional HPLC system consists of a precolumn connected to a six-port switching valve which is on-line with an analytical column. The direct injection of the biological samples onto the precolumn previously equilibrated with 15% acetonitrile allows the elimination of interfering substances. The samples purified on the precolumn can then be eluted onto the analytical column via the switching valve for neuropeptide separation. This trace-enrichment system allows a minimum of sample handling, both saving time and reducing possibilities of loss and contamination. This method has been applied to monitor the precursor and mature forms of atrial natriuretic factor from chromaffin cell secretion media and cell content extracts. The recovery of atrial natriuretic factor is in the range of 80-100%. This procedure could be applied to the study of the precursor-product relationship of any neuropeptide, e.g., from radiolabeled extracts of pulse-chase experiments performed on cultured chromaffin cells.

Animals↗
PubMed1989

Kinetic modeling of the recA protein promoted renaturation of complementary DNA strands.

Quantitative agarose gel assays reveal that the recA protein promoted renaturation of complementary DNA strands (phi X DNA) proceeds in two stages. The first stage results in the formation of unit-length duplex DNA as well as a distribution of other products ("initial products"). In the second stage, the initial products are converted to complex multipaired DNA structures ("network DNA"). In the presence of ATP, the initial products are formed within 2 min and are then rapidly converted to network DNA. In the absence of ATP, the initial products are formed nearly as fast as with ATP present, but they are converted to network DNA at a much lower rate. The time-dependent formation of initial products and network DNA from complementary single strands for both the ATP-stimulated and ATP-independent reactions can be modeled by using a simple two-step sequential kinetic scheme. This model indicates that the primary effect of ATP in the recA protein promoted renaturation reaction is not on the initial pairing step (which leads to the formation of initial products) but rather is to increase the rate at which subsequent pairing events can occur.

Adenosine Triphosphate↗
PubMed1989

Rapid evaluation of tetanus immunity by a haemagglutination test in the injured at a hospital emergency unit.

A turkey red blood cell haemagglutination assay (TRBC HA) allowing rapid measurement of the antibodies against tetanus has been set recently. Its feasibility was evaluated in injured patients admitted into an emergency unit during summer 1987. TRBC HA was performed by the same physician who questioned the patient on his/her previous vaccinations and evaluated his/her immunization status. The rapid HA test practiced in emergency was controlled by TRBC HA and ELISA measurement of antibodies carried out in the laboratory. Each method was compared to the others: the results were fitted and no significant difference was found. The preventive procedures which would have followed the antibody measurement by immediate TRBC HA were compared to the decision resulting from clinical evaluation. The immunoprophylactic attitude would have been the same in 82% of cases. TRBC HA is a reliable test, and feasible in an emergency: it could help in making the appropriate decision for immunoprophylaxis to be applied to the injured and other patients at risk of tetanus.

Animals↗
PubMed1989

Aldosterone secretion inhibitory factor: a novel neuropeptide in bovine chromaffin cells.

We report the identification and the primary structure of a novel neuroendocrine peptide which inhibits aldosterone secretion. The peptide was isolated from 1.5 x 10(10) cultured bovine chromaffin cells by reversed phase and ion exchange HPLC. It is chromatographically and structurally distinct from atrial natriuretic factor (ANF), which we formely identified in chromaffin tissue. This new Aldosterone Secretion Inhibitory Factor (ASIF) is predominant in cultured chromaffin cells and cross-reacts with ANF receptor sites involved in the inhibition of aldosterone production in zona glomerulosa cells. The sequence of this 35-amino acid peptide includes the shorter fragment isolated from porcine brain confirming its neuropeptide character. ASIF might be involved in concert with ANF in the paracrine regulation of aldosterone secretion and the presence of both peptides in cultured chromaffin cells indicates that this system can be used as a model for studying natriuretic neuropeptide production.

Adrenal Glands↗
PubMed1989

Regulation of aldosterone biosynthesis by Na+/H+ antiport: relationships between intracellular pH and angiotensin II.

Recent studies on the regulation of aldosterone biosynthesis have revealed that inhibitors of sodium influx, e.g. amiloride, can inhibit adrenal steroidogenesis with a pharmacological profile suggestive of a Na+/H+ antiport system. We have examined the existence of a Na+/H+ antiport system and its regulation of Na influx and intracellular pH (pHi) in bovine adrenal zona glomerulosa cells. NH4Cl-induced 22Na uptake by zona glomerulosa cells was dose dependently inhibited by ethylisopropylamiloride (EIPA), amiloride, and benzamil with ED50 values of 0.02, 4.30, and 199 microM, respectively. Angiotensin II (AII; 100 nM) caused an initial transient acidification, followed by prolonged alkalinization. The hormone equipotently increased pHi and stimulated aldosterone secretion, with ED50 values of 1.2 and 1.4 nM, respectively. AII-induced alkalinization was suppressed by EIPA, amiloride, and benzamil, with ED50 values of 0.6, 79, and 440 microM, respectively. This increase in pHi induced by AII was dependent upon the extracellular sodium concentration (ED50 values = 2.8 mM) and was blunted in sodium-free medium. AII-stimulated aldosterone synthesis was also inhibited by EIPA, amiloride, and benzamil, with ED50 values of 0.07, 34, and 330 microM, respectively. The time course of activation by angiotensin II on aldosterone secretion was also dependent upon extracellular sodium concentration during a 2-h period. These results document that intracellular pH is regulated through the Na+/H+ exchange system and suggest that the pH change induced by AII might be associated with its regulation of steroidogenesis in bovine adrenal zona glomerulosa cells.

Aldosterone↗
PubMed1989

Purification and primary structure of pro-aldosterone secretion inhibitory factor from bovine adrenal chromaffin cells.

This report documents the purification and the complete primary structure of bovine aldosterone secretion inhibitory factor precursor (pro-ASIF). ASIF-(1-103) contains at position 69-103 of its carboxy-terminal end the formely identified 35-amino acid biologically active form, hence confirming the endogenous character of ASIF in the adrenal medulla. Compared to atrial natriuretic factor (ANF)-related peptide precursors, bovine ASIF displays 65% homology at the carboxy-terminal while the remaining amino-terminal part shows much more variability. Bovine pro-ASIF exhibits 73% homology with porcine pro-brain natriuretic peptide (BNP), a situation reminiscent of the relationship of pro-ANF in various species. When ANF- and BNP-related COOH-termini of bovine, porcine, human, rat, and chicken are compared, it appears that bovine ASIF and porcine BNP are closely related and belong to the same family which however appears to be much more heterogenous than the ANF-related family. These results strongly suggest that bovine ASIF is encoded by a precursor gene similar to the gene of BNP but different from the one encoding ANF.

Adrenal Medulla↗
PubMed1989

Distinct properties of atrial natriuretic factor receptor subpopulations in epithelial and fibroblast cell lines.

We have characterized two atrial natriuretic factor (ANF) receptor subtypes, designated ANF-R1 and ANF-R2, in two established cell lines that express exclusively one receptor subtype. The ANF-R1 receptor is selectively expressed by the kidney epithelial cell line LLC-PK1. It is a 130-kDa protein that has a much higher affinity for the biologically active forms of ANF than for its metabolites. The binding of ANF to this subtype is potentiated by amiloride and by divalent cations. The activation of the ANF-R1 receptor leads to an accumulation of cyclic GMP that is only partially inhibited by methylene blue. The ANF-R2 receptor, which is expressed selectively by the fibroblast cell line NIH-3T3, is a 130-kDa protein composed of two disulfide-linked subunits of 64-kDa. Activation of this subtype by saturating concentrations of ANF does not appear to elicit cyclic GMP production. However, supraphysiological concentrations of ANF induce a nonsaturable accumulation of cyclic GMP with an apparent ED50 in the high micromolar range. In contrast to the ANF-R1 subtype, the stimulation of cyclic GMP production is completely abolished by methylene blue. This subtype recognizes the active forms of ANF as well as its metabolites, and the binding is insensitive to amiloride and is decreased by divalent cations. These two cell lines can serve as models for studying the differential regulatory properties of ANF-R1 and ANF-R2 subtypes. In addition, we have also characterized the two ANF receptor subtypes in rat kidney glomeruli, where they show the same structure and pharmacological characteristics as in the two model cell lines.

Amiloride↗
PubMed1988

New Achromobacter collagenase and its immunological relationship with a vertebrate collagenase.

Evidence is presented that Achromobacter iophagus produces two distinct collagenases. Achromobacter collagenases A and B were separated by high-performance liquid chromatography from partially purified enzyme. The main collagenase, A (EC 3.4.24.8), which has been already described, was eluted in the region of molecular mass 110-90 kDa. A minor collagenase B eluted in the region of 320 kDa, although in SDS-gel electrophoresis the apparent molecular masses of its main active forms were estimated as 55 and 110 kDa. The specificities of collagenases A and B are different. Collagenase A splits in its synthetic substrate Pz-Pro-Leu-Gly-Pro-DArg the bond Leu-Gly, collagenase B does not split this substrate. Both collagenases split bonds Gln-Gly and Leu-Gly in synthetic peptides DNP-Pro-Gln-Gly-Ile-Ala-Gly-Gln-DArg-OH and DNP-Pro-Leu-Gly-Ile-Ala-Gly-DArg-NH2, respectively. Collagenase B is twice as active as A on the native collagen type I. Both enzymes are inhibited by EDTA. The antibodies raised against the human tooth collagenase specifically inhibited the collagenase B, but did not influence the activity of collagenase A. These results indicate, to our knowledge for the first time, an immunological relationship between a bacterial and a vertebrate collagenase.

Amino Acid Sequence↗
PubMed1988

Secretion and biosynthesis of atrial natriuretic factor by cultured adrenal chromaffin cells.

In our previous work, the existence of the precursor and mature forms of atrial natriuretic factor (ANF) within the bovine chromaffin granules has been reported. To confirm the endogenous character of these peptides, we demonstrate that nicotinic activation and depolarization by KCl increase their co-secretion from cultured chromaffin cells. The increase of intracellular levels of these atrial peptides by phorbol ester is potentiated by addition of forskolin. The release of ANF and their de novo synthesis within the cultured chromaffin cells emphasize the usefulness of this model in the study of the mechanisms of release and storage of these peptides in the neuronal tissues.

Adrenal Medulla↗
PubMed1988

Metal Ion Interactions with Phosphoenolpyruvate Carboxylase from Crassula argentea and Zea mays.

Metal ion interactions with phosphoenolpyruvate carboxylase from the CAM plant Crassula argentea and the C(4) plant Zea mays were kinetically analyzed. Fe(2+) and Cd(2+) were found to be active metal cofactors along with the previously known active metals Mg(2+), Mn(2+), and Co(2+). In studies with the Crassula enzyme, Mg(2+) yielded the highest V(max) value but also generated the highest values of K(m) ((metal)) and K(m) ((pep)). For these five active metals lower K(m) ((metal)) values tended to be associated with lower K(m) ((pep)) values. PEP saturation curves showed more kinetic cooperativity than the corresponding metal saturation curves. The activating metal ions all have ionic radii in the range of 0.86 to 1.09 A. Ca(2+), Sr(2+), Ba(2+), and Ni(2+) inhibited competitively with respect to Mg(2+), whereas Be(2+), Cu(2+), Zn(2+), and Pd(2+) showed mixed-type inhibition. V(max) trends with the five active metals were similar for the C. argentea and Z. mays enzymes except that Cd(2+) was less effective with the maize enzyme. K(m) ((metal)) values were 10- to 60-fold higher in the enzyme from Z. mays.

Journal Article↗
PubMed1988

Relation between renal and hepatic excretion of drugs. XI. Excretion of sulfonamides with various physico-chemical properties of different ages--influence of nephrectomy or bile duct ligation.

The pharmacokinetics of a series of 6-sulfonamides, with gradually increasing molecular weights, were studied in anaesthetized rats after intravenous bolus injection. Immature (20-day-old) and adult (55-day-old) rats were compared. In both age groups renal excretion of all sulfonamides tested here dominates (about 5- to 10-fold). In 20-day-old rats renal and hepatic excretions are immature and reach about 50% (liver) or 30% (kidney) of adult values. Relation between renal and hepatic excretion of sulfonamides is strongly correlated to the lipophilicity of these substances. Hepatic excretion of sulfonamides seems to be correlated to their pKa-values. Concerning their excretion via urine it is necessary to correlate different steps of renal transport to physico-chemical properties in detail. A general correlation between renal excretion of sulfonamides and their chemical structure obviously does not exist. After bile duct ligation 24 h before clearance experiments no compensatory increase of renal sulfonamide excretion occurs. 24 h following bilateral nephrectomy hepatic excretion of sulfonamides is significantly enhanced; however, this phenomenon is related to physico-chemical properties of the sulfonamides. Age differences in compensation of one elimination pathway do not exist.

Aging↗
PubMed1987

Rate of degradation of [alpha]- and [beta]-oligodeoxynucleotides in Xenopus oocytes. Implications for anti-messenger strategies.

End-labelled oligodeoxynucleotides were injected into Xenopus laevis oocytes and their degradation products were analysed by high-performance ion-exchange liquid chromatography after various times of incubation. The oligonucleotides were synthesised with either the natural [beta] anomers or the synthetic [alpha] anomers of deoxynucleotide units. Oligo-[beta] deoxynucleotides are short-lived inside oocytes (half-life approximately equal to 10 min). Covalent attachment of an intercalating agent to the 3'-phosphate and of a methylthiophosphate group at the 5'-end protects oligodeoxynucleotides against 3'- and 5'-exonucleases, respectively. The half-life of such substituted oligodeoxynucleotides is increased to 40 minutes. Oligo-[alpha]-deoxynucleotides are quite resistant to both endo and exonucleases inside Xenopus oocytes. After 8 hours only 40% of a 16-mer oligo-[alpha]-deoxynucleotide were hydrolysed. The rapid degradation of oligo-[beta]-deoxynucleotides suggests that efficient inhibition of translation in Xenopus oocytes involves an RNase H-induced hydrolysis of mRNAs hybridized to oligo-[beta]-deoxynucleotides.

Acridines↗
PubMed1987

Sequence-targeted chemical modifications of nucleic acids by complementary oligonucleotides covalently linked to porphyrins.

Oligo-heptathymidylates covalently linked to porphyrins bind to complementary sequences and can induce local damages on the target molecule. In dark reactions, iron porphyrin derivatives exhibited various chemical reactivities resulting in base oxidation, crosslinking and chain scission reactions. Reactions induced by reductants, such as ascorbic acid, dithiothreitol or mercapto-propionic acid, led to very localised reactions. A single base was the target for more than 50% of the damages. Oxidising agents such as H2O2 and its alkyl derivatives induced reactions that extended to a wider range of altered bases. The specificity of the chemical modifications observed in these systems is discussed from a mechanistic point of view.

Alkylating Agents↗